title: Dabrafenib in the treatment of advanced melanoma.
abstract: Advanced melanoma has long been a challenging malignancy to treat due to a relative paucity of efficacious therapeutic options. However, the identification of activating BRAF mutations in approximately 50% of patients with cutaneous melanoma has ushered in the era of targeted therapy for melanoma patients. Similar to the first-in-class selective serine/threonine-protein kinase B-raf inhibitor vemurafenib, dabrafenib is highly efficacious in melanoma patients with BRAF V600E mutations, with response rates of approximately 50% and progression-free survival of 6 months. There is data to suggest that dabrafenib not only shows activity in V600E-mutated melanoma, but also in non-V600E BRAF-mutated disease such as V600K. There is also early data to suggest that dabrafenib is effective in controlling metastases in the brain. Combining dabrafenib with the selective mitogen-activated protein kinase kinase (MEK) inhibitor trametinib has been effective in improving both the progression-free survival and overall survival of melanoma patients over those patients treated with dabrafenib alone. Dabrafenib is still being evaluated in several clinical trials in melanoma as well as a variety of other solid tumors with BRAF mutations. The U.S. Food and Drug Administration has recently approved dabrafenib as a single agent for the treatment of unresectable or metastatic melanoma in adult patients with BRAF V600E mutation.
authors.affiliation: Division of Hematology and Oncology, University of Colorado Cancer Center, Aurora, Colorado, USA.
authors.forename: T
authors.initials: T
authors.lastname: Medina
authors.forename: M N
authors.initials: MN
authors.lastname: Amaria
authors.forename: A
authors.initials: A
authors.lastname: Jimeno
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004347:Drug Interactions; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D008545:Melanoma / Q000188:drug therapy*; D010091:Oximes / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D007093:Imidazoles; D010091:Oximes; D048493:Proto-Oncogene Proteins B-raf; C561627:dabrafenib
keywords: BRAF; Dabrafenib; Melanoma; Targeted therapy